The apparent diffusion coefficient (ADC) of choline-containing compounds (Cho), creatine and phosphocreatine (Cre), N-acetyl-aspartate (NAA), lactate, and water was measured in normal rat brain, and in the ischemic and contralateral region of rat brain approximately 3 and 24 h after induction of focal cerebral ischemia. After 3 h of ischemia, the ADC of Cre and NAA in the ischemic region had significantly decreased by 29% and 19%, respectively (P < 0.05). Lactate ADC was also obtained in the ischemic region. After 24 h of focal ischemia, no ADC values could be measured for NAA, Cre and Cho in the ischemic region because their concentrations had become too low. The ADCs of lactate and water in the ischemic volume were virtually identical at 3 and 24 h after occlusion. The experiments suggest that the ADC decrease of water after induction of ischemia is partly caused by changes in the diffusion characteristics of the intracellular compartment.

The present review has been compiled to highlight the role of magnetic resonance imaging (MRI) and MR spectroscopy (MRS) for the investigation of cerebral ischemia in the animal experimental field of basic research. We have focused on stroke investigations analyzing the pathomechanisms of the disease evolution and on new advances in both nuclear MR (NMR) methodology or genetic engineering of transgenic animals for the study of complex molecular relationships and causes of the disease.

A number of amphipathic peptides were tested for their effects on structural and functional properties of isolated rat liver mitochondria. The peptides included the matrix targeting sequence of subunit IV of (yeast) cytochrome c oxidase. Titration experiments in which the mitochondria were incubated with increasing concentrations of the peptides revealed two major stages in the interaction. First, at low peptide/mitochondria ratios, peptide binding to the outer membrane occurred which was accompanied by gradual lysis of the outer membrane at higher ratios. The latter was deduced from the release of adenylate kinase, the classical marker enzyme of the intermembrane space. Secondly, at still higher peptide/mitochondria ratios, the permeability of the inner membrane progressively increased, as evidenced by measurements of respiratory control and of the membrane potential. Complete uncoupling of respiration seemed to precede dissipation of the membrane potential.

We explored the therapeutic potentials of two N-methyl-D-aspartate (NMDA) receptor antagonists in vivo using different techniques. NMDA injected into the striatum of neonatal rats (20 nmol/0.5 microliters) induced a rapid increase in the diffusion-weighted (DW) image intensity, spreading over a large part of the ipsilateral hemisphere. Subcutaneous injection of the NMDA receptor antagonist MK-801 (1 mg/kg) or D-(E)-4-(3-phosphono-2-prop-enyl)-2-piperazine-carboxylic acid (D-CPPene; 1.5 mg/kg) reversed both the volume and the grading of the NMDA-induced hyperintensity of DW images, the reversal by MK-801 being more rapid than that by D-CPPene. In the cerebral cortex, there was an inverse relationship between changes in DW image intensity and the size of the extracellular space, assessed by electrical impedance measurements. The reduction of the hyperintense volume in DW images 1 or 2 h after MK-801 or D-CPPene treatment of NMDA-injected animals depended on the type of antagonist used and on the interval between intrastriatal NMDA injection and antagonist treatment. The reduction was 95% when MK-801 was given with a delay of 90 min and decreased to 20% when it was given at 360 min. With D-CPPene, the reduction was 80% after a delay of 30 min and virtually absent when it was administered at 360 min. Quantitative analysis showed significant correlations between the residual hyperintense volume 1 or 2 h after MK-801 or D-CPPene treatment and the final lesion volume, assessed from either T2-weighted images (R = 0.89, p < 0.001) or histology (R = 0.80, p < 0.001) 5 days after the insult. This study illustrates the sensitivity of DW magnetic resonance imaging to monitor in vivo early events after an excitotoxic insult and the effect of putative protective drugs that may counteract the resulting damage.

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